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dc.contributor.authorMilon, B.
dc.contributor.authorMitra, S.
dc.contributor.authorSong, Y.
dc.date.accessioned2019-06-05T18:28:16Z
dc.date.available2019-06-05T18:28:16Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85043569185&doi=10.1186%2fs13293-018-0171-0&partnerID=40&md5=fceca2d19e19cd79f8ec280409705413
dc.identifier.urihttp://hdl.handle.net/10713/9428
dc.description.abstractBackground: Noise-induced hearing loss (NIHL) is the most prevalent form of acquired hearing loss and affects about 40 million US adults. Among the suggested therapeutics tested in rodents, suberoylanilide hydroxamic acid (SAHA) has been shown to be otoprotective from NIHL; however, these results were limited to male mice. Methods: Here we tested the effect of SAHA on the hearing of 10-week-old B6CBAF1/J mice of both sexes, which were exposed to 2 h of octave-band noise (101 dB SPL centered at 11.3 kHz). Hearing was assessed by measuring auditory brainstem responses (ABR) at 8, 16, 24, and 32 kHz, 1 week before, as well as at 24 h and 15-21 days following exposure (baseline, compound threshold shift (CTS) and permanent threshold shift (PTS), respectively), followed by histologic analyses. Results: We found significant differences in the CTS and PTS of the control (vehicle injected) mice to noise, where females had a significantly smaller CTS at 16 and 24 kHz (p < 0.0001) and PTS at 16, 24, and 32 kHz (16 and 24 kHz p < 0.001, 32 kHz p < 0.01). This sexual dimorphic effect could not be explained by a differential loss of sensory cells or synapses but was reflected in the amplitude and amplitude progression of wave I of the ABR, which correlates with outer hair cell (OHC) function. Finally, the frequency of the protective effect of SAHA differed significantly between males (PTS, 24 kHz, p = 0.002) and females (PTS, 16 kHz, p = 0.003), and the magnitude of the protection was smaller in females than in males. Importantly, the magnitude of the protection by SAHA was smaller than the effect of sex as a biological factor in the vehicle-injected mice. Conclusions: These results indicate that female mice are significantly protected from NIHL in comparison to males and that therapeutics for NIHL may have a different effect in males and females. The data highlight the importance of analyzing NIHL experiments from males and females, separately. Finally, these data also raise the possibility of effectors in the estrogen signaling pathway as novel therapeutics for NIHL. Copyright 2018 The Author(s).en_US
dc.description.sponsorshipThis work was supported by R01DC03544 (NIDCD), R01DC013817 (NIDCD), and MR130240 (CDMRP/DoD).en_US
dc.description.urihttps://dx.doi.org/10.1186/s13293-018-0171-0en_US
dc.language.isoen-USen_US
dc.publisherBioMed Central Ltd.en_US
dc.relation.ispartofBiology of Sex Differences
dc.subjectABRen_US
dc.subjectB6CBAF1/J miceen_US
dc.subjectInner earen_US
dc.subjectNoise-induced hearing lossen_US
dc.subjectSAHAen_US
dc.subjectSex differencesen_US
dc.titleThe impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in miceen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s13293-018-0171-0
dc.identifier.pmid29530094


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